DISCUSSION
The patient exhibited elongation of the eyelashes and nasal hairs (vibrissae) secondary to panitumumab therapy. The mechanism behind this effect has still not been fully elucidated, although it is related to EGFR inhibition.6 It is known that EGFR is expressed in the skin and hair follicles and plays an important role in the normal development of these body parts.2 Therefore, EFGR inhibition may frequently generate toxicity.
EGFR is a transmembrane glycoprotein found in cells of epithelial origin. It has three components: an extracellular ligand binding domain, a transmembrane region, and an intracellular tyrosine-kinase domain. EFGR inhibitors may function as a monoclonal antibody, acting in the extracellular medium as panitumumab, or in the intracellular medium as tyrosine-kinase inhibitors.7
EFGR inhibitors have been associated with side-effects such as hypertrichosis, alopecia, and changes in hair pigmentation, growth, and texture. These effects are not as common as skin manifestations.7 The severity of skin eruptions may be ameliorated with skin care, topical antibiotics, immunomodulating agents, prophylactic use of tetracyclin and minocyclin, avoiding dose reduction, or discontinuation of drug treatment.4,5 In contrast, eyelash trichomegaly is not a drug-limiting adverse effect nor does it interfere with drug action.2
Eyelash trichomegaly may be congenital or acquired. It has also been observed in patients with Oliver-McFarlane syndrome, oculocutanous type I albinism, systemic infection, or oncologic patients. Furthermore, this adverse reaction has been perceived by patients undergoing oncology treatment with monoclonal antibodies against EGFR, such as cetuximabe or panitumumab.7
These drugs inhibit EGFR, which is expressed on hair follicle epithelium. Therefore, it is believed that trichomegaly is attributable to EGFR inhibition, leading to premature maturation of epithelial cells of the hair follicle, resulting in deregulated gene expression of keratin.7
This side effect appears after 3 weeks of treatment and may occur up to 8 months after initiatiation of therapy with EGFR inhibitor. The onset of effect occurs at a median time period of 12 weeks.7
Elongation of the eyelashes, although not severe, causes a number of problems in a patient’s life, such as discomfort during blinking, difficulty when wearing eyeglasses, and even the occurrence of corneal conditions, eg, erosions, irritation, infections, scarring, and ulcers. The condition may be managed cosmetically with trichotomy to improve symptoms experienced by patients. Furthermore, this adverse effect is probably related to a better prognosis, and may be used as a surrogate clinical marker.² Trichomegaly is a side-effect that does not contraindicate continuous treatment with EGFR inhibitors.6,8
EGFR is a transmembrane glycoprotein found in cells of epithelial origin. It has three components: an extracellular ligand binding domain, a transmembrane region, and an intracellular tyrosine-kinase domain. EFGR inhibitors may function as a monoclonal antibody, acting in the extracellular medium as panitumumab, or in the intracellular medium as tyrosine-kinase inhibitors.7
EFGR inhibitors have been associated with side-effects such as hypertrichosis, alopecia, and changes in hair pigmentation, growth, and texture. These effects are not as common as skin manifestations.7 The severity of skin eruptions may be ameliorated with skin care, topical antibiotics, immunomodulating agents, prophylactic use of tetracyclin and minocyclin, avoiding dose reduction, or discontinuation of drug treatment.4,5 In contrast, eyelash trichomegaly is not a drug-limiting adverse effect nor does it interfere with drug action.2
Eyelash trichomegaly may be congenital or acquired. It has also been observed in patients with Oliver-McFarlane syndrome, oculocutanous type I albinism, systemic infection, or oncologic patients. Furthermore, this adverse reaction has been perceived by patients undergoing oncology treatment with monoclonal antibodies against EGFR, such as cetuximabe or panitumumab.7
These drugs inhibit EGFR, which is expressed on hair follicle epithelium. Therefore, it is believed that trichomegaly is attributable to EGFR inhibition, leading to premature maturation of epithelial cells of the hair follicle, resulting in deregulated gene expression of keratin.7
This side effect appears after 3 weeks of treatment and may occur up to 8 months after initiatiation of therapy with EGFR inhibitor. The onset of effect occurs at a median time period of 12 weeks.7
Elongation of the eyelashes, although not severe, causes a number of problems in a patient’s life, such as discomfort during blinking, difficulty when wearing eyeglasses, and even the occurrence of corneal conditions, eg, erosions, irritation, infections, scarring, and ulcers. The condition may be managed cosmetically with trichotomy to improve symptoms experienced by patients. Furthermore, this adverse effect is probably related to a better prognosis, and may be used as a surrogate clinical marker.² Trichomegaly is a side-effect that does not contraindicate continuous treatment with EGFR inhibitors.6,8
CONCLUSIONS
Eyelash trichomegaly is an unusual side-effect associated with
the use of EFGR inhibitors. These drugs are used in the treatment
of oncology patients and are represented by humanized
monoclonal antibodies or tyrosine-kinase inhibitors. Elongation
of the eyelashes may generate discomfort and ocular sequelae,
mainly due to cosmetic issues, and can be managed with trichotomy.
Nevertheless, when therapy is discontinued, the eyelashes
usually cease to grow and often return to their original length.
DISCLOSURES
The authors report no conflicts.
REFERENCES
1. Morris LGT, Hochster HS, DeLacure MD. Eyelash trichomegaly secondary to panitumumab therapy. Curr Oncol. 2011;18(3):145–6.
2. Ürün Y, Utkan G. Cetuximab related eyelash elongations for patients with metastatic rectum carcinoma: Metabolic complete response. Ann Dermatol. 2013.
3. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425- 1433.
4. Ocvirk J, Cencelj S. Management of cutaneous side-effects of cetuximab therapy in patients with metastatic colorectal cancer. J Eur Acad Dermatol Venereol. 2010;24:453-459.
5. Saif MW, Kim R. Incidence and management of cutaneous toxicities associated with cetuximab. Expert Opin Drug Saf. 2007;6:175-182.
6. Morris LG, Hochster HS, Delacure MD. Eyelash trichomegaly secondary to panitumumab therapy. Curr Oncol. 2011;18(3):145–146. doi:10.3747/ co.v18i3.762
7. Cohen PR, Escudier SM, Kurzrock R. (2011). Cetuximab-associated elongation of the eyelashes. Am J Clin Dermatol. 12(1), 63–67.doi:10.2165/11531920- 000000000-00000
8. Goel V, Raina S, Chandragouda D, et al. Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas. Int J Trichology. 2014;6(1):23–24. doi:10.4103/0974-7753.136755
2. Ürün Y, Utkan G. Cetuximab related eyelash elongations for patients with metastatic rectum carcinoma: Metabolic complete response. Ann Dermatol. 2013.
3. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425- 1433.
4. Ocvirk J, Cencelj S. Management of cutaneous side-effects of cetuximab therapy in patients with metastatic colorectal cancer. J Eur Acad Dermatol Venereol. 2010;24:453-459.
5. Saif MW, Kim R. Incidence and management of cutaneous toxicities associated with cetuximab. Expert Opin Drug Saf. 2007;6:175-182.
6. Morris LG, Hochster HS, Delacure MD. Eyelash trichomegaly secondary to panitumumab therapy. Curr Oncol. 2011;18(3):145–146. doi:10.3747/ co.v18i3.762
7. Cohen PR, Escudier SM, Kurzrock R. (2011). Cetuximab-associated elongation of the eyelashes. Am J Clin Dermatol. 12(1), 63–67.doi:10.2165/11531920- 000000000-00000
8. Goel V, Raina S, Chandragouda D, et al. Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas. Int J Trichology. 2014;6(1):23–24. doi:10.4103/0974-7753.136755
AUTHOR CORRESPONDENCE
Danilo da Fonseca Reis Silva MD MSc oncodanilo@gmail.com
